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Nevin Manimala Statistics

Identifying and handling unbalanced baseline characteristics in a non-randomized, controlled, multicenter social care nurse intervention study for patients in advanced stages of cancer

BMC Cancer. 2022 May 18;22(1):560. doi: 10.1186/s12885-022-09646-6.

ABSTRACT

PURPOSE: Given the psychosocial burdens patients in advanced stages of cancer face, innovative care concepts are needed. At the same time, such vulnerable patient groups are difficult to reach for participation in intervention studies and randomized patient inclusion may not be feasible. This article aims to identify systematic biases respectively selection effects occurring during the recruitment phase and to discuss their potential causes based on a non-randomized, multicenter intervention study with patients in advanced stages of cancer.

METHODS: Patients diagnosed with at least one of 16 predefined cancers were recruited at four hospitals in three German cities. The effect of social care nurses’ continuous involvement in acute oncology wards was measured by health-related quality of life (EORTC QLQ-C30), information and participation preferences, decisional conflicts, doctor-patient communication, health literacy and symptom perception. Absolute standardized mean difference was calculated as a standardized effect size to test baseline characteristics balance between the intervention and control groups.

RESULTS: The study enrolled 362 patients, 150 in the intervention and 212 in the control group. Except for gender, both groups differed in relevant socio-demographic characteristics, e.g. regarding age and educational background. With respect to the distribution of diagnoses, the intervention group showed a higher symptom burden than the control group. Moreover, the control group reported better quality of life at baseline compared to the intervention group (52.6 points (SD 21.7); 47.8 points (SD 22.0), ASMD = 0.218, p = 0.044).

CONCLUSION: Overall, the intervention group showed more social and health vulnerability than the control group. Among other factors, the wide range of diagnoses included and structural variation between the recruiting clinics increased the risk for bias. We recommend a close, continuous monitoring of relevant social and health-related characteristics during the recruitment phase as well as the use of appropriate statistical analysis strategies for adjustment, such as propensity score methods.

TRIAL REGISTRATION: German Clinical Trials Register (DRKS-ID: DRKS00013640 ); registered on 29th December 2017.

PMID:35585571 | DOI:10.1186/s12885-022-09646-6

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Effect of sedative premedication with oral midazolam on postanesthesia care unit delirium in older adults: a secondary analysis following an uncontrolled before-after design

Perioper Med (Lond). 2022 May 19;11(1):18. doi: 10.1186/s13741-022-00253-4.

ABSTRACT

BACKGROUND: Sedative premedication with benzodiazepines has been linked with prolonged recovery and inadequate emergence during the immediate postoperative period. We aimed to analyze the association between postanesthesia care unit (PACU) delirium and sedative premedication with oral midazolam.

METHODS: We performed a secondary analysis of prospectively collected data before (midazolam cohort) and after (non-midazolam cohort) implementation of a restrictive strategy for oral premedication with midazolam. From March 2015 until July 2018, we included patients 60 years and older, who underwent elective radical prostatectomy for prostate cancer. Exclusion criteria were contraindications to premedication with midazolam, preoperative anxiety, and a history of neurological disorders. Patients, who were scheduled for postoperative admission to the intensive care unit, were excluded. Between 2015 and 2016, patients received 7.5 mg oral midazolam preoperatively (midazolam cohort). Patients included between 2017 and 2018 did not receive any sedative medication preoperatively (non-midazolam cohort). The primary endpoint was the incidence of PACU delirium.

RESULTS: PACU delirium rates were 49% in the midazolam cohort (n = 214) and 33% in the non-midazolam cohort (n = 218). This difference was not statistically significant on multivariable logistic regression analysis (OR 0.847 [95% CI 0.164; 4.367]; P = 0.842). Age (OR 1.102 [95% CI 1.050; 1.156]; P < 0.001), the cumulative dose of sufentanil (OR 1.014 [95% CI 1.005; 1.024]; P = 0.005), and propofol-sufentanil for anesthesia maintenance (OR 2.805 [95% CI 1.497; 5.256]; P = 0.001) were significantly associated with PACU delirium.

CONCLUSION: Midazolam for sedative premedication was not significantly associated with PACU delirium. The reduction in the incidence of PACU delirium throughout the study period may be attributable to improvements in perioperative management other than a more restrictive preoperative benzodiazepine administration.

PMID:35585564 | DOI:10.1186/s13741-022-00253-4

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Nevin Manimala Statistics

Medical specialist distributions in Ecuador: a geographical and temporal analysis of data from 2000 to 2017

BMC Health Serv Res. 2022 May 19;22(1):671. doi: 10.1186/s12913-022-08056-5.

ABSTRACT

BACKGROUND: Knowledge of medical specialists’ numbers and geographical distribution are essential for planning health services and health workforce supply. However, although the distribution of physicians is a significant concern for society and policymakers in Ecuador, no studies have evaluated the distribution of specialists in the country. This study aimed to explore the geographical and temporal distribution of medical specialists in Ecuador over 18 years from 2000 to 2017 and analyse its implications for health planning and medical training.

METHODS: We conducted an ecological time-series study based on the National Statistical Register of Resources and Health Activities data. This register provides administrative information for health professionals working in public and private health institutions. Rates of medical specialists by year, geographical area, and speciality were estimated. We used joint-point analyses to identify time trends for medical specialists and physicians in training.

RESULTS: From 2000 to 2017, medical specialists grew from 2737 to 10,929. The rate of medical specialists per 10,000 population increased from 4 in 2000 to 10.3 in 2017. Based on Joint point analysis, two temporal trends were identified. Between 2000 to 2015, specialists increased by 4.1% per year, and between 2015 and 2017, they increased by 20% per year. For the entire study period, three cities (Quito, Guayaquil, and Cuenca) accounted for more than 50% of the specialists in the country. However, medical specialists in other cities and rural areas increased from 37% in 2000 to 46% in 2017. The provinces of Esmeraldas, Carchi, Bolívar and Los Ríos presented rates of less than 6 specialists per 10,000 population by 2017. Of the 46 medical specialities identified by 2017, three represented more than 30% of the professionals (gynaecology 12%, paediatrics 11% and family and community health 8.4%).

CONCLUSIONS: This study shows that the number of medical specialists in Ecuador has increased significantly over the last two decades, although with inequalities in the distribution of specialists between provinces and regions. The results of this study provide background for the Ecuadorian health system when introducing Human Resources of Health (HRH) policies.

PMID:35585557 | DOI:10.1186/s12913-022-08056-5

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Nevin Manimala Statistics

Robust functional principal component analysis via a functional pairwise spatial sign operator

Biometrics. 2022 May 18. doi: 10.1111/biom.13695. Online ahead of print.

ABSTRACT

Functional principal component analysis (FPCA) has been widely used to capture major modes of variation and reduce dimensions in functional data analysis. However, standard FPCA based on the sample covariance estimator does not work well if the data exhibits heavy-tailedness or outliers. To address this challenge, a new robust functional principal component analysis approach based on a functional pairwise spatial sign (PASS) operator, termed PASS FPCA, is introduced. We propose robust estimation procedures for eigenfunctions and eigenvalues. Theoretical properties of the PASS operator are established, showing that it adopts the same eigenfunctions as the standard covariance operator and also allows recovering ratios between eigenvalues. We also extend the proposed procedure to handle functional data measured with noise. Compared to existing robust FPCA approaches, the proposed PASS FPCA requires weaker distributional assumptions to conserve the eigenspace of the covariance function. Specifically, existing work are often built upon a class of functional elliptical distributions, which requires inherently symmetry. In contrast, we introduce a class of distributions called the weakly functional coordinate symmetry (weakly FCS), which allows for severe asymmetry and is much more flexible than the functional elliptical distribution family. The robustness of the PASS FPCA is demonstrated via extensive simulation studies, especially its advantages in scenarios with non-elliptical distributions. The proposed method was motivated by and applied to analysis of accelerometry data from the Objective Physical Activity and Cardiovascular Health Study, a large-scale epidemiological study to investigate the relationship between objectively measured physical activity and cardiovascular health among older women. This article is protected by copyright. All rights reserved.

PMID:35583919 | DOI:10.1111/biom.13695

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Endovascular Perfusion Augmentation for Critical Care Decreases Vasopressor Requirements while Maintaining Renal Perfusion

Shock. 2022 May 1;57(5):740-748. doi: 10.1097/SHK.0000000000001917.

ABSTRACT

BACKGROUND: Ischemia reperfusion injury causes a profound hyperdynamic distributive shock. Endovascular perfusion augmentation for critical care (EPACC) has emerged as a hemodynamic adjunct to vasopressors and crystalloid. The objective of this study was to examine varying levels of mechanical support for the treatment of ischemiareperfusion injury in swine.

METHODS: Fifteen swine underwent anesthesia and then a controlled 30% blood volume hemorrhage followed by 30 min of supra-celiac aortic occlusion to create an ischemia-reperfusion injury Animals were randomized to standardized critical care (SCC), EPACC with low threshold (EPACC-Low), and EPACC with high threshold (EPACC-High). The intervention phase lasted 270 min after injury Hemodynamic markers and laboratory values of ischemia were recorded.

RESULTS: During the intervention phase, SCC spent 82.4% of the time avoiding proximal hypotension (>60 mm Hg), while EPACC-Low spent 97.6% and EPACC-High spent 99.5% of the time avoiding proximal hypotension, P < 0.001. Renal artery flow was statistically increased in EPACC-Low compared with SCC (2.29 mL/min/kg vs. 1.77 mL/ min/kg, P < 0.001), while renal flow for EPACC-High was statistically decreased compared with SCC (1.25 mL/min/kg vs. 1.77 mL/min/kg, P < 0.001). EPACC animals required less intravenous norepinephrine, (EPACC-Low: 16.23mcg/kg and EPACC-High: 13.72 mcg/kg), compared with SCC (59.45 mcg/kg), P = 0.049 and P = 0.013 respectively.

CONCLUSIONS: Compared with SCC, EPACC-High and EPACC-Low had decreased norepinephrine requirements with decreased frequency of proximal hypotension. EPACC-Low paradoxically had increased renal perfusion despite having a mechanical resistor in the aorta proximal to the renal arteries. This is the first description of low volume mechanical hemodynamic support in the setting of profound shock from ischemia-reperfusion injury in swine demonstrating stabilized proximal hemodynamics and augmented distal perfusion.

PMID:35583914 | DOI:10.1097/SHK.0000000000001917

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Inflammasome-related Markers upon ICU Admission do not Correlate with Outcome in Critically Ill COVID-19 Patients

Shock. 2022 May 1;57(5):672-679. doi: 10.1097/SHK.0000000000001923.

ABSTRACT

PURPOSE: The development of targeted biological therapies for coronavirus disease 2019 (COVID-19) requires reliable biomarkers that could help indicate how patients are responding. The hyperactivation of inflammasomes by the SARS-CoV2 virus is hypothesized to contribute to a more severe course of the COVID-19 disease. Therefore, we aimed to evaluate the prognostic value of several inflammasome-related cytokines and proteins upon admission to the intensive care unit (ICU).

PATIENTS AND METHODS: We performed a prospective cohort study. Plasma samples were obtained from 45 critically ill COVID-19 patients and 10 patients without any signs of infection (traumatic brain injury [TBI]) on admission to the ICU. Concentrations of IL-1a, IL-1β, IL-18, IL-1RA, galectin-1, apoptosis-associated speck-like proteins, LDH, ferritin, and gasdermin D were analyzed. A cell-free caspase-1 plasma assay was done by inhibitor-based immunoprecipitation followed by a Western Blot. Demographic and clinical characteristics were recorded.

RESULTS: Inhospital mortality in COVID-19 patients was 62%. Galectin-1 was 1.8-fold lower in COVID-19 than in TBI patients (17101.84 pg/mL vs. 30764.20 pg/mL, P = 0.007), but other inflammasome-related biomarkers had similar concentrations. Patients with a Sequential Organ Failure Assessment (SOFA) score of > 9 on admission who were at high risk of death had significantly higher galectin-1 but lower IL-1RA in comparison with low-risk patients (25551.3 pg/mL vs. 16302.7 pg/mL, P = 0.014; 14.5 pg/mL vs. 39.4pg/mL, P = 0.04, respectively). Statistically significant correlations were observed between: IL-1a and platelets (r = -0.37), IL-1 β and platelets (r = -0.36), ferritin and INR (r = 0.39). Activated caspase-1 p35, whose presence was related to higher fibrinogen and lower D-dimers, was detected in 12 out of 22 COVID-19 patients and in none of the TBI patients. Moreover, densitometric analysis showed a significantly higher amount of p35 in patients with a SOFA score > 9.

CONCLUSION: We found that the systemic markers of activation of inflammasomes in critically ill COVID-19 patients were not directly related to outcome. Therefore, potential interventions aimed at the inflammasome pathway in this group of patients may be of limited effectiveness and should be biomarker-guided.

PMID:35583911 | DOI:10.1097/SHK.0000000000001923

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Clinical, Brain, and Multilevel Clustering in Early Psychosis and Affective Stages

JAMA Psychiatry. 2022 May 18. doi: 10.1001/jamapsychiatry.2022.1163. Online ahead of print.

ABSTRACT

IMPORTANCE: Approaches are needed to stratify individuals in early psychosis stages beyond positive symptom severity to investigate specificity related to affective and normative variation and to validate solutions with premorbid, longitudinal, and genetic risk measures.

OBJECTIVE: To use machine learning techniques to cluster, compare, and combine subgroup solutions using clinical and brain structural imaging data from early psychosis and depression stages.

DESIGN, SETTING, AND PARTICIPANTS: A multisite, naturalistic, longitudinal cohort study (10 sites in 5 European countries; including major follow-up intervals at 9 and 18 months) with a referred patient sample of those with clinical high risk for psychosis (CHR-P), recent-onset psychosis (ROP), recent-onset depression (ROD), and healthy controls were recruited between February 1, 2014, to July 1, 2019. Data were analyzed between January 2020 and January 2022.

MAIN OUTCOMES AND MEASURES: A nonnegative matrix factorization technique separately decomposed clinical (287 variables) and parcellated brain structural volume (204 gray, white, and cerebrospinal fluid regions) data across CHR-P, ROP, ROD, and healthy controls study groups. Stability criteria determined cluster number using nested cross-validation. Validation targets were compared across subgroup solutions (premorbid, longitudinal, and schizophrenia polygenic risk scores). Multiclass supervised machine learning produced a transferable solution to the validation sample.

RESULTS: There were a total of 749 individuals in the discovery group and 610 individuals in the validation group. Individuals included those with CHR-P (n = 287), ROP (n = 323), ROD (n = 285), and healthy controls (n = 464), The mean (SD) age was 25.1 (5.9) years, and 702 (51.7%) were female. A clinical 4-dimensional solution separated individuals based on positive symptoms, negative symptoms, depression, and functioning, demonstrating associations with all validation targets. Brain clustering revealed a subgroup with distributed brain volume reductions associated with negative symptoms, reduced performance IQ, and increased schizophrenia polygenic risk scores. Multilevel results distinguished between normative and illness-related brain differences. Subgroup results were largely validated in the external sample.

CONCLUSIONS AND RELEVANCE: The results of this longitudinal cohort study provide stratifications beyond the expression of positive symptoms that cut across illness stages and diagnoses. Clinical results suggest the importance of negative symptoms, depression, and functioning. Brain results suggest substantial overlap across illness stages and normative variation, which may highlight a vulnerability signature independent from specific presentations. Premorbid, longitudinal, and genetic risk validation suggested clinical importance of the subgroups to preventive treatments.

PMID:35583903 | DOI:10.1001/jamapsychiatry.2022.1163

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The Course of General Cognitive Ability in Individuals With Psychotic Disorders

JAMA Psychiatry. 2022 May 18. doi: 10.1001/jamapsychiatry.2022.1142. Online ahead of print.

ABSTRACT

IMPORTANCE: Schizophrenia is associated with major cognitive deficits and has been conceptualized as both a neurodevelopmental and a neurodegenerative disorder. However, when deficits develop and how they change over the course of illness is uncertain.

OBJECTIVE: To trace cognition from elementary school to old age to test neurodevelopmental and neurodegenerative theories of psychotic disorders.

DESIGN, SETTING, AND PARTICIPANTS: Data were taken from the Suffolk County Mental Health Project, a first-admission longitudinal cohort study of individuals with psychotic disorders. Participants were recruited from all 12 inpatient psychiatric facilities in Suffolk County, New York. This analysis concerns the 428 participants with at least 2 estimates of general cognitive ability. Data were collected between September 1989 and October 2019, and data were analyzed from January 2020 to October 2021.

EXPOSURES: Psychiatric hospitalization for psychosis.

MAIN OUTCOMES AND MEASURES: Preadmission cognitive scores were extracted from school and medical records. Postonset cognitive scores were based on neuropsychological testing at 6-month, 24-month, 20-year, and 25-year follow-ups.

RESULTS: Of the 428 included individuals (212 with schizophrenia and 216 with other psychotic disorders), 254 (59.6%) were male, and the mean (SD) age at psychosis onset was 27 (9) years. Three phases of cognitive change were observed: normative, declining, and deteriorating. In the first phase, cognition was stable. Fourteen years before psychosis onset, those with schizophrenia began to experience cognitive decline at a rate of 0.35 intelligence quotient (IQ) points per year (95% CI, 0.29-0.42; P < .001), a significantly faster decline than those with other psychotic disorders (0.15 IQ points per year; 95% CI, 0.08-0.22, P < .001). At 22 years after onset, both groups declined at a rate of 0.59 IQ points per year (95% CI, 0.25-0.94; P < .001).

CONCLUSIONS AND RELEVANCE: In this cohort study, cognitive trajectories in schizophrenia were consistent with both a neurodevelopmental and neurodegenerative pattern, resulting in a loss of 16 IQ points over the period of observation. Cognitive decline began long prior to psychosis onset, suggesting the window for primary prevention is earlier than previously thought. A window for secondary prevention emerges in the third decade of illness, when cognitive declines accelerate in individuals with schizophrenia and other psychotic disorders.

PMID:35583896 | DOI:10.1001/jamapsychiatry.2022.1142

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Contrast-to-Noise Ratios to Evaluate the Detection of Glaucomatous Progression in the Superior and Inferior Hemiretina

Transl Vis Sci Technol. 2022 May 2;11(5):20. doi: 10.1167/tvst.11.5.20.

ABSTRACT

PURPOSE: To determine the sensitivity of optical coherence tomography (OCT) and standard automated perimetry (SAP) for detecting glaucomatous progression in the superior and inferior hemiretina.

METHODS: We calculated contrast-to-noise ratios (CNRs) for OCT retinal nerve fiber layer (RNFL) thickness of hemiretinas and for SAP mean total deviation (MTD) of the corresponding hemifields from longitudinal data (205 eyes, 125 participants). The glaucoma stage for each hemiretina was based on the corresponding hemifield’s MTD. Contrast was defined as the difference of the parameter between two consecutive glaucoma stages, whereas noise was the measurement variability of the parameter in those stages. The higher the CNR of a parameter, the more sensitive it is to detecting progression in the transition between successive stages.

RESULTS: There were no statistically significant differences for the RNFL CNR and MTD CNR between superior and inferior hemiretinas. As the glaucoma stage of the opposite hemiretina worsened, the MTD CNR in the transition from moderate to advanced glaucoma significantly increased. The RNFL CNR in the transition from mild to moderate glaucoma significantly decreased in case of advanced glaucoma in the opposite hemiretina.

CONCLUSIONS: Similar to full retinas, detecting conversion to glaucoma in hemiretinas is more sensitive with OCT than SAP, whereas with more advanced disease, SAP is more sensitive for detecting progression. More importantly, the sensitivity for detecting progression in one hemiretina with either technique depends on the glaucoma severity in the opposite hemiretina.

TRANSLATIONAL RELEVANCE: Monitoring glaucomatous progression with either OCT or SAP partly depends on the glaucoma severity in the opposite hemiretina.

PMID:35583886 | DOI:10.1167/tvst.11.5.20

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Neural underpinnings of the slowness of information processing in patients with traumatic brain injury: insights from tract-based spatial statistics

Neurol Sci. 2022 May 18. doi: 10.1007/s10072-022-06150-4. Online ahead of print.

ABSTRACT

Slowness of information processing (SIP) is frequently reported after traumatic brain injury (TBI). Previous studies point toward a pivotal role of white matter damage on speed of information processing. However, little is known about the more comprehensive and ecological assessment of SIP in TBI. Here, we combined an ecological assessment of SIP with the use of tract-based spatial statistics (TBSS) on individuals’ fractional anisotropy (FA) maps. Twenty-six moderate-to-severe patients with TBI (21 males and 5 females) participated in this study: 10 individuals were classified as not having SIP (SIP-) and 16 were classified as having SIP (SIP +). SIP + showed lower FA in bilateral anterior thalamic radiation, corticospinal tract, cingulum, and forceps, as well as in bilateral inferior fronto-occipital, inferior and superior longitudinal fasciculi and uncinate fasciculus. Overall, this result is consistent with and expands previous reports on information processing speed to a more comprehensive and ecological perspective on SIP in TBI.

PMID:35583841 | DOI:10.1007/s10072-022-06150-4